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Reproduction Abstracts (2016) 3 P035 | DOI: 10.1530/repabs.3.P035

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Female reproductive ageing: When during oogenesis do chromosomes begin to fall apart?

Randy Ballesteros Mejia, Lisa Lister, Daniel Cooney & Mary Herbert

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Newcastle Fertility Centre, Institute of Genetic Medicine, Newcastle University, Newcastle upon Tyne, UK.


Introduction: During female fetal life, mammalian oocytes begin meiosis and arrest in prophase of meiosis I when they become enclosed in primordial follicles. Bivalent chromosomes established during this time have to remain intact until they are resolved during anaphase I, just before ovulation. Bivalents are stabilized throughout this period by Rec8-containing cohesin complexes. In women, however, extending this period for more than 35 years increases the risk of aneuploidy resulting in infertility, miscarriage and birth defects. Previous studies in our laboratory on fully-grown mouse oocytes indicate that the age-related increase of segregation errors during meiosis I is accompanied by the depletion of chromosomal Rec8 levels. This depletion is accompanied by destabilization of the bivalent chromosome architecture. Nevertheless, the mechanisms and timing of cohesin depletion remain unknown.

Methods: We investigate the possibility that premature cohesin loss could be caused by leaky inhibition of the protease separase, which cleaves Rec8 during anaphase, using a separase knockout mouse model. Also, using Rec8-myc mouse model we explore which stage of oocyte development is susceptible to cohesin loss during age.

Results and discussion: Our results indicate that the loss of cohesin during age also occurs in separase deficient mouse oocytes. Additionally, we found that chromosome-associated cohesin is lost from oocytes at the primordial follicle stage. Together, these results suggest that age-related loss of cohesin occurs during the prolonged prophase-arrest at the primordial follicle stage by a separase-independent mechanism.

Volume 3

Society for Reproduction and Fertility Annual Conference 2016

Winchester, UK
11 Jul 2016 - 11 Jul 2016

Society for Reproduction and Fertility 

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